The applicant proposes to understand the role of monocytotropism in primate lentiviral pathogenicity by exploring the following specific aims. 1). Identify physiologic changes in macrophages that are prompted by HIV infection and, in particular how chemokines influence macrophage-lymphocyte interaction; 2). Define the role of viral gene products, especially Nef, in chemokine release, and 3). Examine in vivo and in vitro phenotype of SIV variants containing non-chemokine inducing Nef alleles and of HIV/SIV variants containing Nef/chemokine substitutions.